1,721,702 research outputs found
Un “Task and Finish Group” dell’”European Federation of Clinical Chemistry and Laboratory Medicine” (EFLM) per la creazione di un nuovo “database” elettronico per i dati di variabilità biologica
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Generation of data on within-subject biological variation in laboratory medicine: an update
No full textIn recent decades, the study of biological variation of laboratory analytes has received increased attention. The reasons for this interest are related to the potential practical applications of such knowledge. Biological variation data allow the derivation of important parameters for the interpretation and use of laboratory tests, such as the index of individuality for the evaluation of the utility of population reference intervals for the test interpretation, the estimate of significant change in a timed series of results of an individual, the number of
specimens required to obtain an accurate estimate of the homeostatic set point of the analyte and analytical performance specifications that assays should fulfill for their application in the clinical setting. It is, therefore, essential to experimentally derive biological variation information in an accurate and reliable way. Currently, a dated guideline for the biological variation data production and a more recent checklist to assist in the correct preparation of
publications related to biological variation studies are available. Here, we update and integrate, with examples, the available guideline for biological variation data production to help researchers to comply with the recommendations of the checklist for drafting manuscripts on biological variation. Particularly, we focus on the distribution of the data, an essential aspect to be considered for the derivation of biological variation data. Indeed, the difficulty in deriving reliable estimates of biological variation for those analytes, the measured concentrations of which are not normally distributed, is more and more evident
Riferibilità metrologica come strumento per la standardizzazione delle misure in Medicina di Laboratorio = Metrological traceability as a tool to standardize measurements in Laboratory Medicine
No full textMetrological traceability as a tool to standardize measurements in Laboratory Medicine. Basics for the correct application of the concept of metrological traceability in laboratory measurements are the univocal definition of the measurand and of an unbroken metrological traceability chain, the demonstration of the commutability of calibration materials, the correction of the measurement bias and the estimate of combined uncertainty at each level of the metrological chain. In vitro diagnostics (IVD) manufacturers should ensure traceability of their analytical systems to recognized higher-order references (materials and/or methods) and estimate the combined uncertainty of calibrators. End-users should check the IVD traceability through the verification that control materials of analytical systems are in the manufacturer’s declared validation range and through the organization of EQAS that meet metrological criteria.
Separately, they should also estimate the contribution to measurement uncertainty by random effects. Main unsolved issues are the lack of full information about sources of traceability and uncertainty of commercial calibrators, the lack of objective analytical specifications and the need to properly define and use ‘traceable’ reference intervals
Standardizzazione della misura e traguardi analitici per l’emoglobina glicata
No full textMeasurement standardization and analytical goals for glycated hemoglobin. Glycated hemoglobin (HbA1c)
plays a key role in diagnosing diabetes and monitoring the glycemic state. To guarantee the reliability of its
measurement at global level, IFCC has defined a reference measurement system, based on the definition of the
measurand as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose
to the N-terminal valine of the hemoglobin β-chain. In addition to the traceability of HbA1c results to the reference system, the establishment of analytical goals to make HbA1c measurements clinically reliable becomes crucial.
However, allowable goals will depend on the assay specificity (i.e., selectivity) and, consequently, on units in which HbA1c results are expressed [mmol/mol for IFCC-aligned systems or % for National Glycohemoglobin Standardization
Program (NGSP) converted numbers]. In this regard, analytical goals derived from biologic variability studies in which the determination of HbA1c has been carried out by an assay providing the same selectivity for the measurand as defined by the IFCC are recommended. Only these targets should be used for evaluating the performance of
commercial assays traceable to the IFCC system and of clinical laboratories using them through appropriately
structured quality controls. Analytical systems following different calibration hierarchies (e.g., the NGSP-aligned
assays) will require different analytical goals
Verification of in vitro medical diagnostics (IVD) metrological traceability : Responsibilities and strategies
No full textTo be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore,
their analytical performance should fulfill acceptable measurement uncertainty criteria defined to fitthe
intended clinical use.With this aim, In Vitro Diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfill during this process uncertainty limits for
calibrators,which should represent a proportion of the uncertainty budget allowed for laboratory results. It is important that end-usersmay know and verify howmanufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. However, full information about traceability and
combined uncertainty of calibrators is currently not available. Important tools for IVD traceability surveillance
are the verification by laboratories of the consistency of declared performance during daily operations performed
in accordance with the manufacturer's instructions and the organization of appropriately structured External
Quality Assessment (EQA) programs. The former activity should be accomplished by analyzing system control materials and confirming that current measurements are in the manufacturer's established control range. With regard to EQA, it is mandatory that target values for materials are assigned with reference procedures by accredited laboratories, thatmaterials are commutable and that a clinically allowable inaccuracy for participant's results is defined
Biologic variability of C-reactive protein : is the available information reliable ?
No full textBackground: C-reactive protein (CRP) is recognized as amarker of cardiovascular risk. The biologic variability of CRP
is crucial to understanding its significance in estimation of individual risk and subsequent changes in serial analyses.
Methods: We systematically reviewed publications on biologic variation of CRP to evaluate the consistency of available data. Data was evaluated with attention to number and type of enrolled subjects, duration of study, frequency of sample collection, sample type, sample storage, analytical methodology, assay sensitivity and statistical analysis.
Results: A total of eleven studies on CRP biologic variability were recruited from literature. The majority of studies
were limited by choice of analytic methodology, population selection, protocol application, and statistical analysis. Unfortunately, the only study that fulfilled all major pre-analytical, analytical and post-analytical requirements derived
biologic variability fromlogarithmically transformed data, thus making application to clinical practice difficult.
Conclusions: There is a paucity of robust data on biologic CRP variability in serum. It is obvious that additional well defined studies are needed to define reliable values of reference change values and of number of samples required to estimate the individual's cardiovascular risk by CRP
The utility of measurement uncertainty in medical laboratories
Full text linkAbstract: The definition and enforcement of reference measurement systems, based on the implementation of metrological traceability of patient results to higherorder (reference) methods and/or materials, together with a clinically acceptable level of measurement uncertainty (MU), are fundamental requirements to produce accurate and equivalent laboratory results. The MU associated with each step of the traceability chain should be governed to obtain a final combined MU on clinical samples fulfilling the requested performance specifications. MU is useful for a number of reasons: (a) for giving objective information about the quality of individual laboratory performance; (b) for serving as a management tool for the medical laboratory and in vitro diagnostics (IVD) manufacturers, forcing them to investigate and eventually fix the identified problems; (c) for helping those manufacturers that produce superior products and measuring systems to demonstrate the superiority of those products; (d) for identifying analytes that need analytical improvement for their clinical use and ask IVD manufacturers to work for improving the quality of assay performance and (e) for abandoning assays with demonstrated insufficient quality. Accordingly, the MU should not be considered a parameter to be calculated by medical laboratories just to fulfill accreditation standards, but it must become a key quality indicator to describe both the performance of an IVD measuring system and the laboratory itself
Verifica della riferibilità metrologica dei dispositivi medico-diagnostici in vitro : responsabilità e strategie
No full textVerification of in vitro medical diagnostics (IVD) metrological traceability: strategies and responsibilities. To be accurate and equivalent laboratory results should be traceable to higher-order references. Furthermore, their analytic quality should fulfil acceptable measurement uncertainty as defined to fit the intended clinical use. To this aim, IVD manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfil during this process uncertainty limits for calibrators that should represent a proportion of the uncertainty budget allowed for clinical laboratory results. It is important that end-users may know and verify how manufacturers
have implemented the traceability of their calibrators and estimated the corresponding uncertainty. Currently, the full information about traceability and uncertainty of calibrator is not available as manufacturers only provide the name of higher-order reference material and/or procedure to which the assay calibration is traceable without any description of steps and their corresponding uncertainty of the implemented traceability chain. Important post-market tools for IVD traceability surveillance are related to the verification by clinical laboratories of the consistency of declared performance during daily operations performed in accordance with the manufacturer’s instructions and the
organization of appropriately structured EQAS. The former activity should be accomplished by analyzing system control materials and confirming that current measurements are in the manufacturer’s established control range. With regard to EQAS, it is mandatory that target values to materials are assigned with reference procedures by an accredited reference laboratory, that materials are commutable and a clinically allowable inaccuracy for participant’s results is defined in order to prove the suitability of laboratory measurements in clinical setting
Implementation of metrological traceability in laboratory medicine: where we are and what is missing
Full text linkBackground: The Joint Committee on Traceability in Laboratory Medicine (JCTLM) has recently created the Task Force on Reference Measurement System Implementation (TF-RMSI) for providing guidance on traceability implementation to in vitro diagnostics (IVD) manufacturers. Using serum creatinine (sCr) as an example, a preliminary exercise was carried out by checking what type of information is available in the JCTLM database and comparing this against derived analytical performance specifications (APS) for measurement uncertainty (MU) of sCr.
Content: APS for standard MU of sCr measurements were established as a fraction (≤0.75, minimum quality; ≤0.50, desirable quality; and ≤0.25, optimum quality) of the intra-individual biological variation of the measurand (4.4%). By allowing no more than one third of the total MU
budget for patient samples to be derived from higher-order references, two out of the four JCTLM reference materials (RMs) at least allow minimum APS to be achieved for the MU of patient samples. Commutability was explicitly assessed for one of the JCTLM-listed matrixed RMs, which was produced in compliance with ISO 15194:2009 standard, whereas the remaining three RMs were assessed against the ISO 15194:2002 version of the standard, which only required the extent of commutability testing to be reported. Regarding the three listed reference methods, the MU associated with isotopic dilution-mass spectrometry coupled to gas chromatography (ID/GC/MS) and
isotopic dilution-mass spectrometry coupled to liquid chromatography (ID/LC/MS) would allow APS to be fulfilled, while the isotope dilution surface-enhanced Raman scattering (ID/SERS) method displays higher MU.
Summary: The most recently listed RM for sCr in the JCTLM database meets the ISO 15194:2009 requirements with MU
that would allow APS to be fulfilled and has had commutability demonstrated for use as a common calibrator in implementing traceability of sCr measurements. Splitting clinical samples with a laboratory performing ID/GC/MS or ID/LC/ MS provides an alternative but would also require all components of uncertainty of these materials to be assessed.
Outlook: Using appropriately derived APS to judge whether reference measurement system components are fit for purpose represents a novel approach. The TF-RMSI is planning to review a greater number of measurands to provide more robust information about the state of the art of available reference measurement systems and their impact on the ability of clinical measurements to meet APS
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